Statistics Of Sequence Comparison

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Work this year focused on an analysis of the effects of various changes in the specification of gap costs on the retrieval accuracy of protein profile search algorithms, with a view towards improving the retrieval accuracy of PSI-BLAST. In brief, the introduction of position-specific substitution costs has greatly improved the sensitivity of protein sequence database search programs: PSI-BLAST and related Hidden Markov Model (HMM) programs are able to recognize much more distant sequence relationships than can BLAST. HMM programs may employ position-specific gap costs as well. By modifying these programs, we found no improvement from position-specific gap costs that took account of the specific amino acids that were inserted or deleted. However, we did find a significant improvement from gap costs that varied according to their location. Incorporating position-specific gap costs into PSI-BLAST requires an accurate description of PSI-BLAST statistics under their use. The most promising path to this goal is the adaptation of the hybrid alignment scoring method for use with PSI-BLAST.